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Chunk #9 — Results — Identification of ctbp-1 as a Mediator of AFT

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Lipid environment modulates the development of acute tolerance to ethanol in Caenorhabditis elegans.
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The eg613 mutation was mapped to the left arm of the X chromosome using SNP mapping methods with the polymorphic wild strain, CB4856 [18], [19]. Using transformation rescue experiments we identified the gene affected by mutation in the eg613 mutant strain as ctbp-1. We found that the eg613 mutation is a splice site mutation in the last nucleotide of intron 9 in the open reading frame of the gene ctbp-1 that is predicted to generate a premature stop codon that results in a truncated protein. A deletion allele of ctbp-1, ok498, failed to complement eg613 for the AFT phenotype, and homozygous ctbp-1(ok498) animals phenocopied eg613 mutants by suppressing the fast development of AFT of npr-1(ky13), tested in a visual assay of speed on ethanol, indicating that ctbp-1 is disrupted by the eg613 mutation. The CTBP-1 protein contains a DNA-binding THAP domain, and CTBP-1 has been shown to act as a negative regulator of transcription [20].